TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6754	20485;20486;20487	chr2:178727105;178727104;178727103	chr2:179591832;179591831;179591830
N2AB	6437	19534;19535;19536	chr2:178727105;178727104;178727103	chr2:179591832;179591831;179591830
N2A	5510	16753;16754;16755	chr2:178727105;178727104;178727103	chr2:179591832;179591831;179591830
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-51
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.4272
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	rs397517494	None	0.959	N	0.451	0.221	0.333154297509	gnomAD-4.0.0	4.91921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.42164E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.2594	likely_benign	0.3958	ambiguous	-0.467	Destabilizing	0.079	N	0.191	neutral	None	None	None	None	N
K/C	0.7993	likely_pathogenic	0.8762	pathogenic	-0.518	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
K/D	0.5488	ambiguous	0.7193	pathogenic	-0.038	Destabilizing	0.969	D	0.599	neutral	None	None	None	None	N
K/E	0.1571	likely_benign	0.2754	benign	0.007	Stabilizing	0.959	D	0.451	neutral	N	0.44437898	None	None	N
K/F	0.8149	likely_pathogenic	0.9049	pathogenic	-0.607	Destabilizing	0.982	D	0.605	neutral	None	None	None	None	N
K/G	0.4647	ambiguous	0.6338	pathogenic	-0.742	Destabilizing	0.884	D	0.53	neutral	None	None	None	None	N
K/H	0.3159	likely_benign	0.4155	ambiguous	-1.208	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
K/I	0.42	ambiguous	0.5763	pathogenic	0.203	Stabilizing	0.884	D	0.609	neutral	None	None	None	None	N
K/L	0.4097	ambiguous	0.5583	ambiguous	0.203	Stabilizing	0.046	N	0.274	neutral	None	None	None	None	N
K/M	0.2577	likely_benign	0.3762	ambiguous	0.309	Stabilizing	0.976	D	0.595	neutral	N	0.507990528	None	None	N
K/N	0.3707	ambiguous	0.5381	ambiguous	-0.123	Destabilizing	0.959	D	0.539	neutral	N	0.474819317	None	None	N
K/P	0.7236	likely_pathogenic	0.8459	pathogenic	0.009	Stabilizing	0.991	D	0.601	neutral	None	None	None	None	N
K/Q	0.1347	likely_benign	0.1922	benign	-0.38	Destabilizing	0.996	D	0.565	neutral	N	0.453097251	None	None	N
K/R	0.0809	likely_benign	0.088	benign	-0.282	Destabilizing	0.959	D	0.46	neutral	N	0.434858207	None	None	N
K/S	0.3333	likely_benign	0.4863	ambiguous	-0.801	Destabilizing	0.759	D	0.475	neutral	None	None	None	None	N
K/T	0.1406	likely_benign	0.2178	benign	-0.576	Destabilizing	0.061	N	0.197	neutral	N	0.43553021	None	None	N
K/V	0.3304	likely_benign	0.4582	ambiguous	0.009	Stabilizing	0.759	D	0.502	neutral	None	None	None	None	N
K/W	0.8061	likely_pathogenic	0.8901	pathogenic	-0.467	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
K/Y	0.6629	likely_pathogenic	0.7971	pathogenic	-0.109	Destabilizing	0.997	D	0.596	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.